CA2523585A1 - Aromatic oxyphenyl and aromatic sulfanylphenyl derivatives - Google Patents
Aromatic oxyphenyl and aromatic sulfanylphenyl derivatives Download PDFInfo
- Publication number
- CA2523585A1 CA2523585A1 CA002523585A CA2523585A CA2523585A1 CA 2523585 A1 CA2523585 A1 CA 2523585A1 CA 002523585 A CA002523585 A CA 002523585A CA 2523585 A CA2523585 A CA 2523585A CA 2523585 A1 CA2523585 A1 CA 2523585A1
- Authority
- CA
- Canada
- Prior art keywords
- alk
- phenoxy
- phenylsulfanyl
- ethyl
- acetic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 125000003118 aryl group Chemical group 0.000 title claims description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 24
- 208000024891 symptom Diseases 0.000 claims abstract description 12
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 248
- -1 1-azepinyl Chemical group 0.000 claims description 106
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 150000002367 halogens Chemical group 0.000 claims description 37
- 238000002360 preparation method Methods 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 230000019771 cognition Effects 0.000 claims description 14
- 206010012289 Dementia Diseases 0.000 claims description 13
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 210000004556 brain Anatomy 0.000 claims description 11
- 150000002431 hydrogen Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 9
- 206010015037 epilepsy Diseases 0.000 claims description 9
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 9
- 208000018198 spasticity Diseases 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 206010010904 Convulsion Diseases 0.000 claims description 8
- 208000002033 Myoclonus Diseases 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 208000014674 injury Diseases 0.000 claims description 8
- 230000008733 trauma Effects 0.000 claims description 8
- 208000030507 AIDS Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 7
- 230000006872 improvement Effects 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 230000003292 diminished effect Effects 0.000 claims description 6
- 208000023516 stroke disease Diseases 0.000 claims description 6
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- 208000035475 disorder Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 3
- 201000004810 Vascular dementia Diseases 0.000 claims description 3
- RFSRESILTCVIRE-INIZCTEOSA-N (2s)-1-[2-[2-(3,4-dichlorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=CC=C1SC1=CC=C(Cl)C(Cl)=C1 RFSRESILTCVIRE-INIZCTEOSA-N 0.000 claims description 2
- QQVXMWFOLKHWBP-INIZCTEOSA-N (2s)-1-[2-[2-(3-fluorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=CC=C1SC1=CC=CC(F)=C1 QQVXMWFOLKHWBP-INIZCTEOSA-N 0.000 claims description 2
- STKOJTYHIUKMDH-INIZCTEOSA-N (2s)-1-[2-[4-chloro-2-(3-fluorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=C(Cl)C=C1SC1=CC=CC(F)=C1 STKOJTYHIUKMDH-INIZCTEOSA-N 0.000 claims description 2
- PPPKGUUFAXPBOP-ZGTCLIOFSA-N 2-[(3r)-3-[2-(3,4-dichlorophenyl)sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CC[C@H]1OC1=CC=CC=C1SC1=CC=C(Cl)C(Cl)=C1 PPPKGUUFAXPBOP-ZGTCLIOFSA-N 0.000 claims description 2
- SELYLOFNFOXBAU-AWKYBWMHSA-N 2-[(3r)-3-[2-[4-(trifluoromethyl)phenyl]sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CC[C@H]1OC1=CC=CC=C1SC1=CC=C(C(F)(F)F)C=C1 SELYLOFNFOXBAU-AWKYBWMHSA-N 0.000 claims description 2
- DSXPIWXOUCHGIJ-UHFFFAOYSA-N 2-[3-[2-(4-tert-butylphenyl)sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CCC1OC1=CC=CC=C1SC1=CC=C(C(C)(C)C)C=C1 DSXPIWXOUCHGIJ-UHFFFAOYSA-N 0.000 claims description 2
- SELYLOFNFOXBAU-UHFFFAOYSA-N 2-[3-[2-[4-(trifluoromethyl)phenyl]sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CCC1OC1=CC=CC=C1SC1=CC=C(C(F)(F)F)C=C1 SELYLOFNFOXBAU-UHFFFAOYSA-N 0.000 claims description 2
- OSFOOQCZEIISLZ-UHFFFAOYSA-N 2-[4-[2-(4-tert-butylphenyl)sulfanylphenoxy]piperidin-1-yl]acetic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1SC1=CC=CC=C1OC1CCN(CC(O)=O)CC1 OSFOOQCZEIISLZ-UHFFFAOYSA-N 0.000 claims description 2
- AYSUNCGFIJZZLO-LBPRGKRZSA-N 2-[[(2s)-1-[2-(3,4-dichlorophenyl)sulfanylphenoxy]propan-2-yl]-methylamino]acetic acid Chemical compound OC(=O)CN(C)[C@@H](C)COC1=CC=CC=C1SC1=CC=C(Cl)C(Cl)=C1 AYSUNCGFIJZZLO-LBPRGKRZSA-N 0.000 claims description 2
- NWSAXYBRKNNYKT-UHFFFAOYSA-N 2-[ethyl-[2-[2-(4-methylsulfanylphenyl)sulfanylphenoxy]ethyl]amino]acetic acid Chemical compound OC(=O)CN(CC)CCOC1=CC=CC=C1SC1=CC=C(SC)C=C1 NWSAXYBRKNNYKT-UHFFFAOYSA-N 0.000 claims description 2
- CCDUYSCWQHZIND-UHFFFAOYSA-N 2-[propan-2-yl-[2-[2-[4-(trifluoromethyl)phenyl]sulfanylphenoxy]ethyl]amino]acetic acid Chemical compound OC(=O)CN(C(C)C)CCOC1=CC=CC=C1SC1=CC=C(C(F)(F)F)C=C1 CCDUYSCWQHZIND-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 22
- 230000000063 preceeding effect Effects 0.000 claims 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- TXBLLCSNAJODAF-KLTJRSTASA-N (2S)-1-[2-(5-chloro-2-phenylsulfanylphenoxy)ethyl]pyrrolidine-2-carboxylic acid (2S)-1-[2-[4-cyano-2-(3-fluorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound ClC=1C=CC(=C(OCCN2[C@@H](CCC2)C(=O)O)C1)SC1=CC=CC=C1.C(#N)C1=CC(=C(OCCN2[C@@H](CCC2)C(=O)O)C=C1)SC1=CC(=CC=C1)F TXBLLCSNAJODAF-KLTJRSTASA-N 0.000 claims 1
- PVQINNCWDICOGZ-OZXSUGGESA-N (2s)-1-[2-[(6s)-6-(3-fluorophenyl)sulfanyl-6-methylsulfonyl-4-phenylcyclohexa-1,3-dien-1-yl]oxyethyl]pyrrolidine-2-carboxylic acid Chemical compound C([C@@]1(S(=O)(=O)C)SC=2C=C(F)C=CC=2)C(C=2C=CC=CC=2)=CC=C1OCCN1CCC[C@H]1C(O)=O PVQINNCWDICOGZ-OZXSUGGESA-N 0.000 claims 1
- ZWUVAZPGHSLJHR-INIZCTEOSA-N (2s)-1-[2-[2-(3-chloro-4-fluorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=CC=C1SC1=CC=C(F)C(Cl)=C1 ZWUVAZPGHSLJHR-INIZCTEOSA-N 0.000 claims 1
- LFGBKELOWUQGSN-QHCPKHFHSA-N (2s)-1-[2-[2-(3-fluorophenyl)sulfanyl-4-(4-methoxyphenyl)phenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(C=C1SC=2C=C(F)C=CC=2)=CC=C1OCCN1[C@H](C(O)=O)CCC1 LFGBKELOWUQGSN-QHCPKHFHSA-N 0.000 claims 1
- MOSALANQQKROEG-FQEVSTJZSA-N (2s)-1-[2-[2-(3-fluorophenyl)sulfanyl-4-morpholin-4-ylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=C(N2CCOCC2)C=C1SC1=CC=CC(F)=C1 MOSALANQQKROEG-FQEVSTJZSA-N 0.000 claims 1
- YHOBMZUBDXFLGN-QFIPXVFZSA-N (2s)-1-[2-[2-(3-fluorophenyl)sulfanyl-4-phenylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=C(C=2C=CC=CC=2)C=C1SC1=CC=CC(F)=C1 YHOBMZUBDXFLGN-QFIPXVFZSA-N 0.000 claims 1
- LRSFEGHEYYCRBC-NRFANRHFSA-N (2s)-1-[2-[2-(3-fluorophenyl)sulfanyl-4-piperidin-1-ylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=C(N2CCCCC2)C=C1SC1=CC=CC(F)=C1 LRSFEGHEYYCRBC-NRFANRHFSA-N 0.000 claims 1
- LRSQEJVDIKQNDF-FQEVSTJZSA-N (2s)-1-[2-[2-(3-fluorophenyl)sulfanyl-4-pyrimidin-5-ylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=C(C=2C=NC=NC=2)C=C1SC1=CC=CC(F)=C1 LRSQEJVDIKQNDF-FQEVSTJZSA-N 0.000 claims 1
- WECFWXVXPQTBPG-FQEVSTJZSA-N (2s)-1-[2-[2-(3-fluorophenyl)sulfanyl-5-thiophen-3-ylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC(C2=CSC=C2)=CC=C1SC1=CC=CC(F)=C1 WECFWXVXPQTBPG-FQEVSTJZSA-N 0.000 claims 1
- PSWRKUIGMUYFGQ-IBGZPJMESA-N (2s)-1-[2-[2-(4-tert-butylphenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1SC1=CC=CC=C1OCCN1[C@H](C(O)=O)CCC1 PSWRKUIGMUYFGQ-IBGZPJMESA-N 0.000 claims 1
- YSZVJUONMPCCKU-INIZCTEOSA-N (2s)-1-[2-[2-[4-(trifluoromethyl)phenyl]sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=CC=C1SC1=CC=C(C(F)(F)F)C=C1 YSZVJUONMPCCKU-INIZCTEOSA-N 0.000 claims 1
- RYSQXDNKDPFOPX-QHCPKHFHSA-N (2s)-1-[2-[4-(4-cyanophenyl)-2-(3-fluorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC=C(C=2C=CC(=CC=2)C#N)C=C1SC1=CC=CC(F)=C1 RYSQXDNKDPFOPX-QHCPKHFHSA-N 0.000 claims 1
- XDFZHBXYNPRYCO-QHCPKHFHSA-N (2s)-1-[2-[5-(4-cyanophenyl)-2-(3-fluorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC(C=2C=CC(=CC=2)C#N)=CC=C1SC1=CC=CC(F)=C1 XDFZHBXYNPRYCO-QHCPKHFHSA-N 0.000 claims 1
- SDQBDJLRIAKRKZ-INIZCTEOSA-N (2s)-1-[2-[5-chloro-2-(3-fluorophenyl)sulfanylphenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCOC1=CC(Cl)=CC=C1SC1=CC=CC(F)=C1 SDQBDJLRIAKRKZ-INIZCTEOSA-N 0.000 claims 1
- GPNZYWGNEOQANA-SFHVURJKSA-N (2s)-1-[3-[2-(3-fluorophenyl)sulfanylphenyl]propyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1CCCC1=CC=CC=C1SC1=CC=CC(F)=C1 GPNZYWGNEOQANA-SFHVURJKSA-N 0.000 claims 1
- WNOAJLDYPRYBGC-KRWDZBQOSA-N (2s)-2-[2-[2-(3-fluorophenyl)sulfanyl-4-phenylphenoxy]ethyl-methylamino]propanoic acid Chemical compound OC(=O)[C@H](C)N(C)CCOC1=CC=C(C=2C=CC=CC=2)C=C1SC1=CC=CC(F)=C1 WNOAJLDYPRYBGC-KRWDZBQOSA-N 0.000 claims 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- JEUCPBIJZMQCSQ-AWKYBWMHSA-N 2-[(3r)-3-[2-(4-chlorophenyl)sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CC[C@H]1OC1=CC=CC=C1SC1=CC=C(Cl)C=C1 JEUCPBIJZMQCSQ-AWKYBWMHSA-N 0.000 claims 1
- UPENMHLUTWVZSA-BZSJEYESSA-N 2-[(3r)-3-[2-(4-methylphenyl)-3-sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CC[C@H]1OC1=CC=CC(S)=C1C1=CC=C(C)C=C1 UPENMHLUTWVZSA-BZSJEYESSA-N 0.000 claims 1
- DSXPIWXOUCHGIJ-UHUGOGIASA-N 2-[(3r)-3-[2-(4-tert-butylphenyl)sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CC[C@H]1OC1=CC=CC=C1SC1=CC=C(C(C)(C)C)C=C1 DSXPIWXOUCHGIJ-UHUGOGIASA-N 0.000 claims 1
- YYZRTMLGELLDJU-KRWDZBQOSA-N 2-[(3s)-3-[2-(4-tert-butylphenyl)sulfanylphenoxy]pyrrolidin-1-yl]acetic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1SC1=CC=CC=C1O[C@@H]1CN(CC(O)=O)CC1 YYZRTMLGELLDJU-KRWDZBQOSA-N 0.000 claims 1
- IGBUJWFABAMDAC-UHFFFAOYSA-N 2-[2-[2-(3-fluorophenyl)sulfanylphenoxy]ethyl-methylamino]acetic acid Chemical compound OC(=O)CN(C)CCOC1=CC=CC=C1SC1=CC=CC(F)=C1 IGBUJWFABAMDAC-UHFFFAOYSA-N 0.000 claims 1
- XNCZVPPVEXAMJM-UHFFFAOYSA-N 2-[2-[[2-(4-methylsulfanylphenyl)sulfanylphenoxy]methyl]piperidin-1-yl]acetic acid Chemical compound C1=CC(SC)=CC=C1SC1=CC=CC=C1OCC1N(CC(O)=O)CCCC1 XNCZVPPVEXAMJM-UHFFFAOYSA-N 0.000 claims 1
- HBFDPGHOXPJXLW-UHFFFAOYSA-N 2-[2-[[2-(4-tert-butylphenyl)sulfanylphenoxy]methyl]piperidin-1-yl]acetic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1SC1=CC=CC=C1OCC1N(CC(O)=O)CCCC1 HBFDPGHOXPJXLW-UHFFFAOYSA-N 0.000 claims 1
- PPPKGUUFAXPBOP-UHFFFAOYSA-N 2-[3-[2-(3,4-dichlorophenyl)sulfanylphenoxy]pyrrolidin-1-yl]propanoic acid Chemical compound C1N(C(C)C(O)=O)CCC1OC1=CC=CC=C1SC1=CC=C(Cl)C(Cl)=C1 PPPKGUUFAXPBOP-UHFFFAOYSA-N 0.000 claims 1
- YYZRTMLGELLDJU-UHFFFAOYSA-N 2-[3-[2-(4-tert-butylphenyl)sulfanylphenoxy]pyrrolidin-1-yl]acetic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1SC1=CC=CC=C1OC1CN(CC(O)=O)CC1 YYZRTMLGELLDJU-UHFFFAOYSA-N 0.000 claims 1
- VGCPLRHDUHCRSI-UHFFFAOYSA-N 2-[4-[2-(3,4-dichlorophenyl)sulfanylphenoxy]piperidin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCC1OC1=CC=CC=C1SC1=CC=C(Cl)C(Cl)=C1 VGCPLRHDUHCRSI-UHFFFAOYSA-N 0.000 claims 1
- CVYFJHQLYYREHZ-CYBMUJFWSA-N 2-[[(2r)-1-[2-(3,4-dichlorophenyl)sulfanylphenoxy]propan-2-yl]-ethylamino]acetic acid Chemical compound OC(=O)CN(CC)[C@H](C)COC1=CC=CC=C1SC1=CC=C(Cl)C(Cl)=C1 CVYFJHQLYYREHZ-CYBMUJFWSA-N 0.000 claims 1
- ZXCFYXRYTQBOPO-AWEZNQCLSA-N 2-[[(2s)-1-[2-(3-chlorophenyl)sulfanylphenoxy]propan-2-yl]-ethylamino]acetic acid Chemical compound OC(=O)CN(CC)[C@@H](C)COC1=CC=CC=C1SC1=CC=CC(Cl)=C1 ZXCFYXRYTQBOPO-AWEZNQCLSA-N 0.000 claims 1
- SKBQSHASAHKUGB-UHFFFAOYSA-N 2-[ethyl-[1-[2-(3-fluorophenyl)sulfanylphenoxy]butan-2-yl]amino]acetic acid Chemical compound OC(=O)CN(CC)C(CC)COC1=CC=CC=C1SC1=CC=CC(F)=C1 SKBQSHASAHKUGB-UHFFFAOYSA-N 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 97
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 95
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 42
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 40
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- 239000000543 intermediate Substances 0.000 description 36
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- 235000019439 ethyl acetate Nutrition 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000005111 ventral hippocampus Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/20—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US46675503P | 2003-04-30 | 2003-04-30 | |
US60/466,755 | 2003-04-30 | ||
DKPA200300649 | 2003-04-30 | ||
DKPA200300649 | 2003-04-30 | ||
PCT/DK2004/000290 WO2004096761A1 (en) | 2003-04-30 | 2004-04-27 | Aromatic oxyphenyl and aromatic sulfanylphenyl derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2523585A1 true CA2523585A1 (en) | 2004-11-11 |
Family
ID=33420360
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002523585A Abandoned CA2523585A1 (en) | 2003-04-30 | 2004-04-27 | Aromatic oxyphenyl and aromatic sulfanylphenyl derivatives |
Country Status (13)
Country | Link |
---|---|
US (1) | US7612068B2 (ko) |
EP (1) | EP1622868A1 (ko) |
JP (1) | JP2006524642A (ko) |
KR (1) | KR20060004967A (ko) |
CN (1) | CN100439330C (ko) |
AU (1) | AU2004233942A1 (ko) |
BR (1) | BRPI0409739A (ko) |
CA (1) | CA2523585A1 (ko) |
CO (1) | CO5640099A2 (ko) |
IS (1) | IS8040A (ko) |
MX (1) | MXPA05011198A (ko) |
NO (1) | NO20055632L (ko) |
WO (1) | WO2004096761A1 (ko) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005100301A1 (en) * | 2004-03-31 | 2005-10-27 | Eli Lilly And Company | 2-aryloxyethyl glycine derivatives and their use as glycine transport inhibitors |
CN101784533B (zh) | 2007-08-22 | 2013-08-21 | 艾博特股份有限两合公司 | 4-苄基氨基喹啉、含有它们的药物组合物和它们在治疗中的用途 |
CN102083797B (zh) | 2008-04-01 | 2014-06-04 | Abbvie公司 | 四氢异喹啉、含有它们的药物组合物和它们在治疗中的用途 |
TW201038569A (en) | 2009-02-16 | 2010-11-01 | Abbott Gmbh & Co Kg | Heterocyclic compounds, pharmaceutical compositions containing them, and their use in therapy |
AR075442A1 (es) | 2009-02-16 | 2011-03-30 | Abbott Gmbh & Co Kg | Derivados de aminotetralina, composiciones farmaceuticas que las contienen y sus usos en terapia |
US8846743B2 (en) | 2010-08-13 | 2014-09-30 | Abbott Laboratories | Aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9045459B2 (en) * | 2010-08-13 | 2015-06-02 | AbbVie Deutschland GmbH & Co. KG | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9051280B2 (en) | 2010-08-13 | 2015-06-09 | AbbVie Deutschland GmbH & Co. KG | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US8877794B2 (en) | 2010-08-13 | 2014-11-04 | Abbott Laboratories | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US8883839B2 (en) | 2010-08-13 | 2014-11-11 | Abbott Laboratories | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9309200B2 (en) | 2011-05-12 | 2016-04-12 | AbbVie Deutschland GmbH & Co. KG | Benzazepine derivatives, pharmaceutical compositions containing them, and their use in therapy |
TW201319049A (zh) | 2011-08-05 | 2013-05-16 | Abbott Gmbh & Co Kg | 胺基□唍、胺基硫□唍及胺基-1,2,3,4-四氫喹啉衍生物,包含彼等之醫藥組合物及彼等於治療之用途 |
US9487476B2 (en) | 2011-10-12 | 2016-11-08 | Yale University | Catechol diethers as potent anti-HIV agents |
US8846741B2 (en) | 2011-11-18 | 2014-09-30 | Abbvie Inc. | N-substituted aminobenzocycloheptene, aminotetraline, aminoindane and phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9365512B2 (en) | 2012-02-13 | 2016-06-14 | AbbVie Deutschland GmbH & Co. KG | Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9656955B2 (en) | 2013-03-15 | 2017-05-23 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9650334B2 (en) | 2013-03-15 | 2017-05-16 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
KR20160062165A (ko) | 2013-10-17 | 2016-06-01 | 아비에 도이치란트 게엠베하 운트 콤파니 카게 | 아미노테트랄린 및 아미노인단 유도체, 이들을 포함하는 약제학적 조성물, 및 치료에서 이들의 용도 |
CN105992764A (zh) | 2013-10-17 | 2016-10-05 | 艾伯维德国有限责任两合公司 | 氨基色满、氨基硫代色满及氨基-1,2,3,4-四氢喹啉衍生物,包含其的药物组合物及其在治疗中的用途 |
US9550754B2 (en) | 2014-09-11 | 2017-01-24 | AbbVie Deutschland GmbH & Co. KG | 4,5-dihydropyrazole derivatives, pharmaceutical compositions containing them, and their use in therapy |
US20180072690A1 (en) * | 2015-03-26 | 2018-03-15 | Cipla Limited | Methods for Making Serotonin Reuptake Inhibitors |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0871440B1 (en) | 1995-12-07 | 2006-03-22 | Daniel C. Javitt | Treatment of negative and cognitive symptoms of schizophrenia with glycine uptake antagonists |
WO1997045115A1 (en) * | 1996-05-31 | 1997-12-04 | Trophix Pharmaceuticals, Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
KR100776119B1 (ko) * | 2000-05-19 | 2007-11-16 | 아스텔라스세이야쿠 가부시키가이샤 | 트리아졸 유도체 |
DOP2001000189A (es) | 2000-06-30 | 2002-03-30 | Pfizer Prod Inc | Benzofenonas y sulfonas como inhibidores de la captación de glicina |
BR0113011A (pt) * | 2000-07-21 | 2003-07-01 | Lundbeck & Co As H | Novos compostos e sua utilização como inibidores de transporte de glicina; composição farmacêutica e método do tratamento |
US20020120149A1 (en) * | 2000-09-08 | 2002-08-29 | Ali Syed M. | Substituted hydrazine derivatives |
WO2002022581A1 (en) * | 2000-09-14 | 2002-03-21 | Gliatech, Inc. | Nitrogen-containing compounds and their use as glycine transport inhibitors |
AR032653A1 (es) * | 2001-02-09 | 2003-11-19 | Telik Inc | Inhibidores heterociclicos del trasportador de glicina 2 composiciones farmaceuticas, uso y metodos. |
US6566550B2 (en) | 2001-06-21 | 2003-05-20 | Pfizer Inc | Substituted aromatic ethers as inhibitors of glycine transport |
DE60206454T2 (de) * | 2001-08-16 | 2006-06-29 | Pfizer Products Inc., Groton | Difluormethylen aromatische Ether und ihre Verwendung als Inhibitoren des Glycin-Typ-1-Transporters |
-
2004
- 2004-04-27 CN CNB2004800112196A patent/CN100439330C/zh not_active Expired - Fee Related
- 2004-04-27 AU AU2004233942A patent/AU2004233942A1/en not_active Abandoned
- 2004-04-27 CA CA002523585A patent/CA2523585A1/en not_active Abandoned
- 2004-04-27 MX MXPA05011198A patent/MXPA05011198A/es unknown
- 2004-04-27 KR KR1020057020543A patent/KR20060004967A/ko not_active Application Discontinuation
- 2004-04-27 JP JP2006504368A patent/JP2006524642A/ja active Pending
- 2004-04-27 WO PCT/DK2004/000290 patent/WO2004096761A1/en active Application Filing
- 2004-04-27 BR BRPI0409739-4A patent/BRPI0409739A/pt not_active Application Discontinuation
- 2004-04-27 EP EP04729612A patent/EP1622868A1/en not_active Withdrawn
- 2004-04-27 US US10/551,737 patent/US7612068B2/en not_active Expired - Fee Related
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2005
- 2005-09-22 IS IS8040A patent/IS8040A/is unknown
- 2005-10-28 CO CO05110325A patent/CO5640099A2/es unknown
- 2005-11-29 NO NO20055632A patent/NO20055632L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
NO20055632L (no) | 2005-11-29 |
IS8040A (is) | 2005-09-22 |
US7612068B2 (en) | 2009-11-03 |
KR20060004967A (ko) | 2006-01-16 |
MXPA05011198A (es) | 2005-12-14 |
CO5640099A2 (es) | 2006-05-31 |
CN1780815A (zh) | 2006-05-31 |
BRPI0409739A (pt) | 2006-05-09 |
EP1622868A1 (en) | 2006-02-08 |
WO2004096761A1 (en) | 2004-11-11 |
JP2006524642A (ja) | 2006-11-02 |
WO2004096761A8 (en) | 2004-12-09 |
AU2004233942A1 (en) | 2004-11-11 |
US20060235003A1 (en) | 2006-10-19 |
CN100439330C (zh) | 2008-12-03 |
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EEER | Examination request | ||
FZDE | Discontinued |